We want to develop new sweetening agents free from the shortcomings of the presently available materials. Sugars are generally high caloric compounds. Diabetic individuals must severely restrict sugar intake. Cyclamates have recently been removed as general sweetening agents because thy have been involved in tumor production in test animals. Even saccharin has been implicated in certain deletorious biological effects. We propose to undertake the synthesis of certain peptide derivatives related to the structure of L-aspartyl-L-phenylalanine methyl ester, a recognized synthetic sweetening agent. It is our aim to prepare a series of analogs which maintain their sweetness, are hydrolytically stable and are metabolically safe. Specifically, we will make retroenantiomers, topochemically similar structures and depsipeptides related to L-aspartyl-L-phenylalanine methyl ester, which has been shown to be 160 times sweeter than sucrose. As part of our program, we will examine the solution properties of the peptide of the peptide derivatives including their conformational analysis. We are in the process of discussing collaborative arrangements for toxicological and controlled taste panel aspects of this research effort. It is our hope that new, biologically safe, highly effective sweeteners will come from this work.